Status epilepticus (SE) is a life-threatening medical emergency that requires prompt recognition and treatment. SE is not a specific disease but rather a manifestation of a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. Adherence is mandatory to the basic principles of neuroresuscitation, the A, B, and Cs, followed by a planned treatment protocol. Proper management requires the identification and treatment of the underlying cause in order to facilitate seizure control and prevent ongoing neurologic injury. Specific clinical and electrographic stages of SE have treatment implications and there are certain special circumstances that require immediate seizure control. This chapter focuses on the evaluation and treatment convulsive SE (CSE), including refractory SE (RSE).

SE is defined as more than 30 minutes of either continuous seizure activity or two or more sequential seizures without full recovery of consciousness in-between.¹ However, treatment starts before this duration. Lowenstein, Bleck, and Macdonald proposed an “operational definition” for treatment of generalized CSE in adults and older children (age >5 years): 5 minutes or more of either a continuous seizure, or two or more discrete seizures between which there is incomplete recovery of consciousness.² These principles apply to all ages.

SE is classified by seizure type, either partial (focal) or generalized as defined by the International Classification of Epileptic Seizures.³ A modified system is based on semiology⁴: CSE or nonconvulsive SE (NCSE). NCSE occurs with either generalized (absence) or focal (partial complex) epilepsy, or as the end stage of CSE. SE is also classified by etiology: acute symptomatic, remote symptomatic, remote symptomatic with acute precipitant, progressive encephalopathy, cryptogenic, idiopathic, and febrile SE.⁵

CSE consists of continuous tonic and/or clonic motor activity, which may be asymmetric, overt, or subtle, with bilateral, although frequently asymmetrical, electroencephalogram (EEG) ictal discharges and altered consciousness^4,6 NCSEs or subtle CSEs have no obvious signs despite marked impairment of consciousness and bilateral EEG discharges,⁶ and may evolve from convulsive SE or its apparent successful treatment. Pseudo-SE also occurs in children.^7,8

The clinical stages of SE are listed in Table 38–1.⁹ The premonitory stage consists of confusion, myoclonus, or increasing seizure frequency; the early stage, continuous seizure activity; subtle CSE or NCSE may develop in the refractory stage. If identified, the premonitory stage is treated. We have delineated special circumstances in the early stage that require immediate seizure control (Table 38–2).¹⁰ The transition stage is actually the time within the early stage when compensatory systems become overwhelmed, which marks the beginning of the late stage. This transition stage differs from patient to patient, depending on the circumstances. EEG stages correlate with the clinical stages¹¹ (Table 38–3). Antiepileptic drug (AED) treatment in the early stage controls seizure activity better than when given later.¹¹ However, not every defined stage occurs in an episode of SE.¹²

Initially, brain compensatory mechanisms, especially hypertension with increased cerebral blood flow (CBF), may prevent neuronal injury. Lothman outlined the systemic and brain metabolic alterations that occur with prolonged SE¹³: hypoxemia, hypercarbia, hypotension, and hyperthermia, with decreased brain oxygen tension, a mismatch between the sustained increase in oxygen and glucose utilization and a fall in CBF and depletion of brain glucose and oxygen. Brain compensation requires adequate airway, breathing, circulation, and CBF and timelines assume that compensatory mechanisms remain intact during the incipient and early stages. However, a higher morbidity and mortality occurs with new-onset inpatient SE, suggesting already compromised compensatory mechanisms.¹⁴ Experimental data also support earlier therapy. In an animal model, both diazepam and phenytoin prevented SE when administered early but efficacy decreased when given later.¹⁵ A loss of inhibitory GABA-A receptors¹⁶ and a functional change in GABA-A receptors occurs^17,18 as the duration of partial SE increases. These findings have also been demonstrated in young animals.¹⁹

The incidence of SE in children ranges from 10 to 58/100,000 per year.^20,21,22,23 In population-based studies of children with epilepsy, the incidence of SE varies from 9.5% to 27%.^24,25,26 SE occurs in the very young, especially in those less than age 2 years, with 80% having an afebrile or acute symptomatic etiology.²⁷ In a study of seizure duration in 407 new onset seizures, two time distributions occurred: (1) 76% had mean seizure duration of 3.6 minutes and (2) 24% had a mean duration of 31 minutes. The longer the seizure lasted, the less likely it would stop within the next several minutes.²⁸ The American Academy of Neurology (AAN) practice parameter retrospectively analyzed 2093 children, excluding neonates, less than the age of 19 years from 20 studies.²⁹ The etiologic categories were assessed (Table 38–4). The occurrence of a remote symptomatic with an acute precipitant episode was low, but this category was not included in the majority of the studies. When included in the prospective London data, called acute on remote, this category was more frequent (Table 38–5).

The North London SE in childhood surveillance study (NLSTEPSS), the first prospective population-based study of CSE in children, identified and prospectively followed 176 children after an initial episode of SE³⁰ (see Chapter 61). The ascertainment adjusted incidence was between 17 and 23/100,000 per year. Ninety-eight were healthy prior to SE (56%) and 56 of these (57%) had a prolonged febrile seizure. The incidence of recurrence within 1 year was 16% and mortality was 3%. The age-adjusted incidence for acute symptomatic SE was 16.9% in those less than 1 year of age, 2.5% in those 1–4 years, and 0.1% in those 5–15 years of age. The incidence of an acute or remote (remote symptomatic with an acute precipitant) was 6%, 5.3%, and 0.7%, respectively. A prolonged febrile seizure occurred in 4.1/100,000, acute symptomatic causes in 2.2/100,000, remote symptomatic in 2.3/100,000, acute on remote in 2.1/100,000, idiopathic in 1.4/100,000, cryptogenic in 0.2/100,000, and unclassified in 1/100,000.

Prognosis depends on etiology, age, duration, and treatment adequacy. Etiology is a very important determinant of morbidity and mortality and the specific cause must be determined and treated in order to prevent ongoing neuronal injury and facilitate seizure control. The disorders causing the acute symptomatic category may require a specific therapy. In a classic study of 239 cases of pediatric SE by Aicardi and Chevrie, 113 cases were symptomatic and 126 were cryptogenic. In those with symptomatic SE, 63/113 (56%) had acute CNS insults, including treatable disorders such as bacterial meningitis, encephalitis, dehydration or electrolyte disorders, toxic ingestions, or subdural hematoma.³¹ In those with cryptogenic SE, 67/126 (53%) were associated with fever (a prolonged, or complex, febrile seizure). In the later study by Maytal et al: 45/193 (23%) were acute symptomatic and 45/193 (23%) were remote symptomatic.³²

The Richmond Study included adults and identified different etiologies for children; the most common cause in adults was cerebrovascular disease (25.2%) whereas fever and infection (35.7%) were more common in children.³³ A recent medication change was a major precipitant of SE in all ages, accounting for 20% of cases in children and 19% in adults.

Acute symptomatic etiologies occur in 17%³⁰ to 23%³² in two modern studies; the most common etiology is prolonged febrile seizures.³⁰ SE is more common in the very young, especially in those less than 2 years, with over 80% of young children having a febrile or acute symptomatic etiology.²⁷ In a population-based study of 226 children, acute bacterial meningitis (ABM) was the most frequent acute symptomatic etiology, followed by viral infections, metabolic disturbances, and head injury.²⁹ ABM was found in 17% of children with CSE and fever.³⁴

Symptomatic SE has a maximum frequency and higher morbidity and mortality in the very young, occurring less frequently after 1 year of age.³⁵ Idiopathic SE is rare during the first several months, becoming more frequent after 6 months. In 31 infants less than 6 months of age, treatable causes included: infectious etiologies in 7%, 1 with pneumococcal meningitis; inborn errors of metabolism in 16%; electrolyte abnormalities in 16%, and trauma in 3%.³⁶ In a recent review, the short-term mortality was 3% to 5%,³⁷ the practice parameter mortality ranged from 4% to 11%.,²⁹ and the NLSTEPSS mortality was 3%.³⁰ The Maytal study had an overall mortality of 4%; occurring only in those with acute symptomatic or progressive symptomatic etiologies.³² There were no deaths in a recent UK retrospective study of 137 children.³⁸ The Richmond study had an overall mortality of 6%.³⁵ When stratified by age, mortality within the first year was 17.8%, but in the first 6 months, mortality was 24% compared to 9% in infants aged 6–12 months. This difference was related to the higher incidence of symptomatic SE in the youngest children.³⁵

With respect to morbidity, a Canadian study reported developmental deterioration in 34% of 40 children after a seizure duration of 30–720 minutes.³⁹ Speech delay has been reported after febrile SE.⁴⁰ Prolonged SE is associated with increased mortality reported as 1.8% in one study⁴¹ a Dutch study of GCSE correlated outcome with treatment adequacy.⁴²

The treatment of SE starts with attention to A, B, and Cs (Table 38–6). Diagnostic studies, obtained after stabilization, are guided by the history, examination, and age, with a greater need to exclude treatable causes in the youngest children. Serum glucose should be rapidly checked to exclude hypoglycemia. CBC may be helpful for infection, although leukocytosis occurs from SE itself.